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Introduction: The microbial community plays a crucial role in the pathological microenvironment. However, the structure of the microbial community within endometriotic lesions and its impact on the microenvironment is still limited. Methods: All 55 tissue samples, including ovarian ectopic (OEMs) and normal (NE) endometrium, were subjected to 16S rRNA sequencing, metabolomic and proteomic analysis. Results: We found the abundance of Tuzzerella is significantly lower in OEMs compared to NE tissue (p < 0.01). We selected samples from these two groups that exhibited the most pronounced difference in Tuzzerella abundance for further metabolomic and proteomic analysis. Our findings indicated that endometriotic lesions were associated with a decrease in l-Glutamine levels. However, proteomic analysis revealed a significant upregulation of proteins related to the complement pathway, including C3, C7, C1S, CLU, and A2M. Subsequent metabolic and protein correlation predictions demonstrated a negative regulation between l-Glutamine and C7. In vitro experiments further confirmed that high concentrations of Glutamine significantly inhibit C7 protein expression. Additionally, immune cell infiltration analysis, multiplex immunofluorescence, and multifactorial testing demonstrated a positive correlation between C7 expression and the infiltration of regulatory T cells (Tregs) in ectopic lesions, while l-Glutamine was found to negatively regulate the expression of chemotactic factors for Tregs. Conclusion: In this study, we found a clear multi-omics pathway alteration, "Tuzzerella (microbe)—l-Glutamine (metabolite)—C7 (protein)," which affects the infiltration of Tregs in endometriotic lesions. Our findings provide insights into endometriosis classification and personalized treatment strategies based on microbial structures. [ABSTRACT FROM AUTHOR]

SLC7A11 has significant translational value in cancer treatment. However, there are few studies on whether SLC7A11 affects the immune status of lung adenocarcinoma (LUAD). Information on SLC7A11 expression and its impact on prognosis was obtained from the cancer genome atlas and gene expression omnibus databases. The differentially expressed genes (DEGs) were analysed by GO and KEGG. GSEA enrichment analysis was performed in the SLC7A11-high and SLC7A11-low groups. The relationship between SLC7A11 and tumour immunity, immune checkpoints, and immune cell infiltration was studied using R language. We analysed the correlation between SLC7A11 and chemotactic factors (CFs) and chemokine receptors using the TISIDB database. SLC7A11 is overexpressed in many tumours, including LUAD. The 5-year overall survival of patients in the SLC7A11-high group was lower than in the SLC7A11-low group. KEGG analysis found that the DEGs were enriched in ferroptosis signaling pathways. GSEA analysis found that the survival-related signaling pathways were enriched in the SLC7A11-low group. The SLC7A11-low group had higher immune scores and immune checkpoint expression. SLC7A11 was negatively correlated with many immune cells (CD8+ T cells, immature dendritic cells), CFs, chemokine receptors (such as CCL17/19/22/23, CXCL9/10/11/14, CCR4/6, CX3CR1, CXCR3) and MHCs (major histocompatibility complex). SLC7A11 may regulate tumour immunity and could be a potential therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. [ABSTRACT FROM AUTHOR]

The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic repair are poorly understood. We developed a model of adaptive and fibrotic kidney regeneration by titrating ischemic injury dose. We performed detailed biochemical and histological analysis and profiled transcriptomic changes at bulk and single-cell level (> 110,000 cells) over time. Our analysis highlights kidney proximal tubule cells as key susceptible cells to injury. Adaptive proximal tubule repair correlated with fatty acid oxidation and oxidative phosphorylation. We identify a specific maladaptive/profibrotic proximal tubule cluster after long ischemia, which expresses proinflammatory and profibrotic cytokines and myeloid cell chemotactic factors. Druggability analysis highlights pyroptosis/ferroptosis as vulnerable pathways in these profibrotic cells. Pharmacological targeting of pyroptosis/ferroptosis in vivo pushed cells towards adaptive repair and ameliorates fibrosis. In summary, our single-cell analysis defines key differences in adaptive and fibrotic repair and identifies druggable pathways for pharmacological intervention to prevent kidney fibrosis. After acute injury, kidneys either successfully repair/regenerate or become fibrotic. Here the authors use scRNA-seq to study adaptive/maladaptive kidney regeneration and identify proinflammatory/fibrotic proximal tubule cells with pharmacologically targetable pyroptosis/ferroptosis signatures. [ABSTRACT FROM AUTHOR]

Primary brain tumors, such as glioblastoma (GBM), are remarkably resistant to immunotherapy, even though pre-clinical models suggest effectiveness. To understand this better in patients, here we take advantage of our recent neoadjuvant treatment paradigm to map the infiltrating immune cell landscape of GBM and how this is altered following PD-1 checkpoint blockade using high dimensional proteomics, single cell transcriptomics, and quantitative multiplex immunofluorescence. Neoadjuvant PD-1 blockade increases T cell infiltration and the proportion of a progenitor exhausted population of T cells found within the tumor. We identify an early activated and clonally expanded CD8+ T cell cluster whose TCR overlaps with a CD8+ PBMC population. Distinct changes are also observed in conventional type 1 dendritic cells that may facilitate T cell recruitment. Macrophages and monocytes still constitute the majority of infiltrating immune cells, even after anti-PD-1 therapy. Interferon-mediated changes in the myeloid population are consistently observed following PD-1 blockade; these also mediate an increase in chemotactic factors that recruit T cells. However, sustained high expression of T-cell-suppressive checkpoints in these myeloid cells continue to prevent the optimal activation of the tumor infiltrating T cells. Therefore, future immunotherapeutic strategies may need to incorporate the targeting of these cells for clinical benefit. Immune-checkpoint blockade has shown limited benefits in patients with glioblastoma. To understand how the composition of the tumor immune microenvironment might limit clinical responses, here the authors present a high dimensional profiling of the immune landscape in patients with glioblastoma following neoadjuvant PD-1 checkpoint blockade. [ABSTRACT FROM AUTHOR]

The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12 receptor CXCR7, but not of the CXCL12 receptor CXCR4. The effect of TFPI on TEM was abolished by the CXCR7 inhibitor, CCX771, while the CXCR4 inhibitor AMD3100 strongly increased TEM. TFPI co-localized with GPC3 on the cell surface. An antibody to GPC3, HS20, decreased CXCR7 expression and abolished the effect of TFPI on TEM. TFPI activated β-catenin and the Wnt/β-catenin inhibitor IWP4 repressed the effect of TFPI on CXCR7 expression and TEM. We conclude that TFPI may contribute to organ infiltration in CLL patients. [ABSTRACT FROM AUTHOR]

This prospective one-year follow-up study was conducted from 835 visits in 178 rheumatoid arthritis (RA) patients. Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months. Radiographs of hands and feet were acquired at baseline and one year. We evaluated the correlation and accuracy of activity scores in predicting remission, HAQ-DI changes and radiographic changes. DAS28-MCP-1 correlated strongly with DAS28-ESR, DAS28-CRP and SDAI scores (0.830, 0.899 and 0.931, respectively, with all P < 0.001). Score changes of DAS28-MCP-1 were comparable to those of DAS28-ESR, DAS28-CRP and SDAI in predicting changes in HAQ-DI and bone erosion. DAS28-MCP-1 (<2.2) was better than DAS28-ESR (<2.6) in indicating modified American Rheumatism Association remission and 2011 American College of Rheumatology/European League Against Rheumatism remission (75.61% vs. 36.99% and 81.71% vs. 49.13%, respectively) with odds ratios of 5.28 and 4.62 (both P < 0.001), respectively. We compared DAS28-MCP-1 with SDAI (≦3.3) in indicating remission with odds ratios of 2.63 (P = 0.002) and 0.98, respectively (and DAS28-MCP-1 with DAS28-CRP < 2.5: 1.33 and 0.92). Therefore, DAS28-MCP-1 is useful as an alternative in assessing RA activity. [ABSTRACT FROM AUTHOR]

Objectives: CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA. Methods: All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019). According to random effects model, standardized mean difference (SMD) and 95% confidence interval (CI) of CXCL13 levels in SLE and RA were calculated by Stata 12.0 software. Results: Totally, 15 studies were selected (981 SLE patients and 380 healthy controls, 332 RA patients and 147 healthy controls). SLE and RA patients were significantly increased in circulating CXCL13 levels (SMD = 1.851, 95% CI 0.604–3.098; SMD = 1.801, 95% CI = 1.145–2.457). Subgroup analyses showed that SLE patients from the Chinese group and systemic lupus erythematosus disease activity index (SLEDAI) score ≥ 6 group had higher circulating CXCL13 levels (SMD = 2.182, 95% CI 0.135–4.229; SMD = 0.767, 95% CI 0.503–1.030). However, there were no significant changes in CXCL13 concentrations in SLE patients from the English and SLEDAI score < 6 group. Similarly, subgroup analyses presented that RA patients from different classifications showed higher circulating CXCL13 levels. There was no publication bias. Conclusions: This meta-analysis demonstrated increased circulating CXCL13 concentrations in SLE and RA patients. Circulating CXCL13 levels may act as biomarkers and therapy targets in the diagnosis and treatment of SLE and RA. Key Point • First, CXC ligand 13 (CXCL13) is closely related to the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), Second, this study may provide novel therapeutic targets for the treatment of SLE and RA patients. This meta-analysis provides a comprehensive analysis of circulating CXCL13 levels in patients with SLE and RA and also explores related influencing factors. [ABSTRACT FROM AUTHOR]

C-X-C motif chemokine 8 (CXCL-8), known as interleukin-8, is a pro-inflammatory cytokine which acts as a chemotactic factor, mainly for leukocytes. CXCL-8 is produced by malignant cells, and therefore it can stimulate the growth and progression of various neoplasms, including oesophageal cancer (OC). The aim of the current study was to measure serum concentrations of chemokine CXCL-8 in OC patients and establish whether this protein might be considered a potential candidate for a tumor marker in the diagnosis and progression of OC. The study included 50 OC subjects (32 patients with squamous cell carcinoma of oesophagus—OSCC, 18 patients with adenocarcinoma—OAC) and 26 healthy volunteers. Serum CXCL-8 concentrations were measured using immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetric method, while classical tumor marker levels were measured using chemiluminescent immunoassay. CXCL-8 concentrations were significantly higher in OC patients compared to healthy controls. We demonstrated significant differences between CXCL-8 concentrations and depth of tumor invasion (T factor) in OC patients and OSCC subgroup. In addition, CXCL-8 levels were found to correlate positively with T factor and CRP concentrations. The diagnostic sensitivity, negative predictive value and the area under ROC curve (AUC) of CXCL-8 were higher than those of classical tumor markers. Our findings suggest the potential usefulness of CXCL-8 in the diagnosis and progression of OC. However, due to the non-specific nature of this chemokine, further research is needed to clarify the usefulness of CXCL-8 as a tumor marker of OC. [ABSTRACT FROM AUTHOR]

Angiogenesis is the process by which new blood vessels form from existing vessels. During angiogenesis, tip cells migrate via diffusion and chemotaxis, new tip cells are introduced through branching, loops form via tip-to-tip and tip-to-sprout anastomosis, and a vessel network forms as endothelial cells, known as stalk cells, follow the paths of tip cells (a process known as the snail-trail). Using a mean-field approximation, we systematically derive one-dimensional non-linear continuum models from a lattice-based cellular automaton model of angiogenesis in the corneal assay, explicitly accounting for cell volume. We compare our continuum models and a well-known phenomenological snail-trail model that is linear in the diffusive, chemotactic and branching terms, with averaged cellular automaton simulation results to distinguish macroscale volume exclusion effects and determine whether linear models can capture them. We conclude that, in general, both linear and non-linear models can be used at low cell densities when single or multi-species exclusion effects are negligible at the macroscale. When cell densities increase, our non-linear model should be used to capture non-linear tip cell behavior that occurs when single-species exclusion effects are pronounced, and alternative models should be derived for non-negligible multi-species exclusion effects. [ABSTRACT FROM AUTHOR]

Anti-Borrelia antibodies in the cerebrospinal fluid (CSF) are required for definite diagnosis of Lyme neuroborreliosis (LNB). However, children often present with early LNB, and antibody production in the CSF may not be demonstrated. Recent studies have suggested the chemokine CXCL13 to be an early marker for LNB. The aim of the study was to evaluate CXCL13 for laboratory diagnosis in pediatric LNB patients and to evaluate the association with pleocytosis in CSF, clinical features, and recovery. CSF samples were collected from LNB patients, classified as definite LNB (n = 44) or possible LNB (n = 22), and controls classified as non-LNB (n = 102) or other specific diagnoses (n = 23). CSF samples were analyzed with the recomBead CXCL13 assay (Mikrogen Diagnostik, Germany), cut-off 160 pg/mL. CXCL13 was significantly higher in LNB patients compared to controls (p < 0.001). Among LNB patients, 58/66 had elevated CXCL13, and among controls, 111/125 had CXCL13 levels under cut-off (sensitivity 88%, specificity 89%). In LNB patients with pleocytosis but no detectable anti-Borrelia antibodies in CSF (possible LNB), CXCL13 was elevated in 16/22 (73%). A weak correlation between CXCL13 and pleocytosis in CSF was found in LNB patients (Rho = 0.46, p < 0.01), but no differences in CXCL13 levels in relation to specific clinical features. In conclusion, CXCL13 is elevated in CSF in children with LNB, showing acceptable sensitivity and specificity. In patients with possible LNB, CXCL13 was elevated in a majority of cases (73%) and is suggested as a complementary diagnostic tool in pediatric LNB patients. CXCL13 was not associated with specific clinical features or recovery. [ABSTRACT FROM AUTHOR]

The goal of this paper is to study the mathematical properties of a new model of soil carbon dynamics which is a reaction-diffusion system with a chemotactic term, with the aim to account for the formation of soil aggregations in the bacterial and microorganism spatial organization (hot spot in soil). This is a spatial and chemotactic version of MOMOS (Modelling Organic changes by Micro-Organisms of Soil), a model recently introduced by M. Pansu and his group. The authors present here two forms of chemotactic terms, first a 'classical' one and second a function which prevents the overcrowding of microorganisms. They prove in each case the existence of a nonnegative global solution, and investigate its uniqueness and the existence of a global attractor for all the solutions. [ABSTRACT FROM AUTHOR]

Monocyte chemotactic protein-induced protein 1(MCPIP1) is identified as an important inflammatory regulator during immune response. MCPIP1 possesses antiviral activities against several viruses, such as Japanese encephalitis. However, its role on Coxsackievirus B3 (CVB3) infection, a positive-stranded RNA virus, has not been addressed. Here, we reported that MCPIP1 was up-regulated in cardiomyocytes by CVB3 infection and in hearts and pancreas of infected mice. Then we found that overexpression of MCPIP1 inhibited CVB3 replication and knockdown of it promoted virus replication. Luciferase assay demonstrated MCPIP1 targeting non-ARE region of CVB3 3′UTR, which was dependent on its RNase, RNA binding and oligomerization abilities, but not deubiquitinase activity. We further verified that MCPIP1 negatively regulated CVB3-induced inflammatory response in macrophages. Thus, our data suggest MCPIP1 as a potent host defense against CVB3 infection and viral myocarditis. [ABSTRACT FROM AUTHOR]

The global existence and the instability of constant steady states are obtained together for a Keller-Segel type chemotactic aggregation model. Organisms are assumed to change their motility depending only on the chemical density but not on its gradient. However, the resulting model is closely related to the logarithmic model, where $\gamma (v):=c_{0}v^{-k}$ is the motility function. The global existence is shown for all chemosensitivity constant $k>0$ with a smallness assumption on $c_{0}>0$ . On the other hand constant steady states are shown to be unstable only if $k>1$ and ${\varepsilon }>0$ is small. Furthermore, the threshold diffusivity ${\varepsilon }_{1}>0$ is found that, if ${\varepsilon }<{\varepsilon }_{1}$ , any constant steady state is unstable and an aggregation pattern appears. Numerical simulations are given for radial cases. [ABSTRACT FROM AUTHOR]

This paper deals with the following chemotaxis-Stokes system under no-flux boundary conditions in a bounded domain $$\Omega \subset \mathbb {R}^{3}$$ with smooth boundary, where $$m\ge 1$$ , $$\phi \in W^{1,\infty }(\Omega )$$ , f and S are given functions with values in $$[0,\,\infty )$$ and $$\mathbb {R}^{3\times 3}$$ , respectively. Here S satisfies $$|S(x,n,c)|\frac{7}{6}$$ , which insures the global existence of bounded weak solution. Our result covers completely and improves the recent result by Wang and Cao (Discrete Contin Dyn Syst Ser B 20:3235-3254, 2015) which asserts, just in the case $$m=1$$ , the global existence of solutions, but without boundedness, and that by Winkler (Calc Var Partial Differ Equ 54:3789-3828, 2015) which only involves the case of $$\alpha =0$$ and requires the convexity of the domain. [ABSTRACT FROM AUTHOR]

Migration is a key cellular function with important implications in cell physiology. Impairment of such function is observed in angiogenesis, cancer, central nervous system development, and many other physiological and pathological events. Serum is considered among the most potent physiological chemotactic stimuli. Transglutaminase 2 (TG2) is involved in most of the mentioned processes, suggesting the hypothesis that TG2 may modulate cell movement and chemotaxis by acting on serum factors. Cell biology and biochemistry studies confirmed this hypothesis, showing that human serum contains potent chemotactic signals significantly impaired by activated TG2. Bioinformatics studies indicated that one potent serum factor potential substrate of TG2-dependent transamidation is platelet-derived growth factor-BB (PDGF-BB). Cell biology and immunometric experiments carried out with U87MG human glioma cell line showed that human recombinant PDGF-BB pre-incubated with calcium-activated TG2 lost about 70 % of its chemotactic activity and antigenicity. These data indicate that PDGF-BB is a substrate of TG2-transamidating activity, and such modification may play a key role in the modulation of PDGF's chemotactic features. Further, these findings suggest a novel point of view to study the extracellular functions of TG2 and to understand how protein signals, such as growth factors and cytokines, act in the extracellular space to reach their specific targets. [ABSTRACT FROM AUTHOR]

In oogamous species of brown algae such as Saccharina japonica and Fucus distichus, the sperm possess an unusual long posterior flagellum, which oscillates actively and produces a propulsive force during swimming. In this study, we quantitatively analyzed the effect of chemotactic responses on sperm swimming and flagellar waveforms by high-speed video recordings. We found that the thigmotactic response to the chemo-attractant was not enhanced during chemotactic swimming and that the swimming velocity of sperm did not decrease. As concentration of the chemo-attractant decreased, the sperm performed drastic U-turn movements, which was caused by a rapid and large bend of the posterior flagellum. Unilateral bending of the posterior flagellum when sensing a decrease in the concentration of the chemo-attractant may be a common response in male gametes during fertilization of brown algae both oogamous and isogamous species. [ABSTRACT FROM AUTHOR]

We consider the finite volume approximation for a non-linear parabolic-elliptic system, which describes the aggregation of slime molds resulting from their chemotactic features, called a simplified Keller-Segel system. First, we present a linear finite volume scheme that satisfies both positivity and mass conservations, which are important features of the original system. We derive some inequalities on the discrete free energy. Then, under some assumptions on the regularity of solution, admissible mesh and a priori estimates of the discrete solution, we establish error estimates in $$L^p$$ norm with a suitable $$p>2$$ for the two dimensional case. In the last part of this paper, we restrict our attention to the radially symmetric solution of chemotaxis system, and we derive some inequalities concerned with the blow-up phenomenon of numerical solution. Several numerical experiments are presented to verify the theoretical results. [ABSTRACT FROM AUTHOR]

In this work, a multilevel thresholding approach that uses modified bacterial foraging optimization (MBFO) is presented for enhancing the applicability and practicality of optimal thresholding techniques. First, the diversity of solutions is considered during the reproduction step. Each weak bacterium randomly selects a strong bacterium from the healthiest bacteria, attempts to reach a location near the chosen strong bacterium, and maintains the same direction. Particle swarm optimization is subsequently incorporated into each chemotactic step to strengthen the global searching capability and quicken the convergence rate of the bacterial foraging algorithm. Finally, the optimal thresholds are obtained by maximizing the Tsallis thresholding functions using the proposed MBFO algorithm. The performance of the proposed algorithm in solving complex stochastic optimization problems is compared with other popular approaches such as a bacterial foraging algorithm, particle swarm optimization algorithm, and genetic algorithm. Experimental results show that the optimal thresholds produced using MBFO require less computation time. The devised algorithm generates more stable results, and the proposed method performs better than the other algorithms in terms of multilevel thresholding. In addition, MBFO method can achieve significantly better results than other compare algorithms on a set of benchmark functions. [ABSTRACT FROM AUTHOR]

Abstract.: Multicellular tumour spheroids (MCTSs) are extensively used as in vitro system models for investigating the avascular growth phase of solid tumours. In this work, we propose a continuous growth model of heterogeneous MCTSs within a porous material, taking into account a diffusing nutrient from the surrounding material directing both the proliferation rate and the mobility of tumour cells. At the time scale of interest, the MCTS behaves as an incompressible viscous fluid expanding inside a porous medium. The cell motion and proliferation rate are modelled using a non-convective chemotactic mass flux, driving the cell expansion in the direction of the external nutrients' source. At the early stages, the growth dynamics is derived by solving the quasi-stationary problem, obtaining an initial exponential growth followed by an almost linear regime, in accordance with experimental observations. We also perform a linear-stability analysis of the quasi-static solution in order to investigate the morphological stability of the radially symmetric growth pattern. We show that mechano-biological cues, as well as geometric effects related to the size of the MCTS subdomains with respect to the diffusion length of the nutrient, can drive a morphological transition to fingered structures, thus triggering the formation of complex shapes that might promote tumour invasiveness. The results also point out the formation of a retrograde flow in the MCTS close to the regions where protrusions form, that could describe the initial dynamics of metastasis detachment from the in vivo tumour mass. In conclusion, the results of the proposed model demonstrate that the integration of mathematical tools in biological research could be crucial for better understanding the tumour's ability to invade its host environment. Graphical abstract: [ABSTRACT FROM AUTHOR]

Using the auxiliary equation method, we obtain exact solutions of certain nonlinear chemotaxis diffusion reaction equations in the presence of a stimulant. In particular, we account for the nonlinearities arising not only from the density-dependent source terms contributed by the particles and the stimulant but also from the coupling term of the stimulant. In addition to this, the diffusion of the stimulant and the effect of long-range interactions are also accounted for in the constructed coupled differential equations. The results obtained here could be useful in the studies of several biological systems and processes, e.g., in bacterial infection, chemotherapy, etc. [ABSTRACT FROM AUTHOR]

Chemotaxis, encystment, cyst germination, and germ tube growth of Phytophthora sojae zoospores in response to common amino acids and sugars in root exudates ( l-glutamate, l-aspartate, l-asparagine, l-alanine, l-serine, l-valine, l-histidine, and l-hydroxyproline; l-glucose, l-sucrose, l-fructose, l-arabinose, and l-galactose were examined. All 8 l-amino acids and 5 l-sugars stimulated zoospore chemotaxis, encystment and cyst germination but did not stimulate subsequent growth of the germ tube in P. sojae. Germ tube growth was significantly retarded in response to each of the test compounds. These findings suggest that chemotaxis, encystment and cyst germination in P. sojae zoospores are receptor-mediated and that the zoospores did not take up and utilize the test amino acids and sugars as nutrients. Different amino acids and sugars affected zoospore chemotaxis to different degrees. Maximum promotion or inhibition occurred at specific concentrations for each compound. [ABSTRACT FROM AUTHOR]

The membrane-anchored glycoprotein RECK (reversion-inducing cysteine-rich protein with Kazal motifs) inhibits expression and activity of certain matrix metalloproteinases (MMPs), thereby suppressing tumor cell metastasis. However, RECK's role in physiological cell function is largely unknown. Human mesenchymal stem cells (hMSCs) are able to differentiate into various cell types and represent promising tools in multiple clinical applications including the regeneration of injured tissues by endogenous or transplanted hMSCs. RNA interference of RECK in hMSCs revealed that endogenous RECK suppresses the transcription and biosynthesis of tissue inhibitor of metalloproteinases (TIMP)-2 but does not influence the expression of MMP-2, MMP-9, membrane type (MT)1-MMP and TIMP-1 in these cells. Knockdown of RECK in hMSCs promoted monolayer regeneration and chemotactic migration of hMSCs, as demonstrated by scratch wound and chemotaxis assay analyses. Moreover, expression of endogenous RECK was upregulated upon osteogenic differentiation and diminished after adipogenic differentiation of hMSCs. RECK depletion in hMSCs reduced their capacity to differentiate into the osteogenic lineage whereas adipogenesis was increased, demonstrating that RECK functions as a master switch between both pathways. Furthermore, knockdown of RECK in hMSCs attenuated the Wnt/β-catenin signaling pathway as indicated by reduced stability and impaired transcriptional activity of β-catenin. The latter was determined by analysis of the β-catenin target genes Dickkopf1 ( DKK1), axis inhibition protein 2 ( AXIN2), runt-related transcription factor 2 ( RUNX2) and a luciferase-based β-catenin-activated reporter (BAR) assay. Our findings demonstrate that RECK is a regulator of hMSC functions suggesting that modulation of RECK may improve the development of hMSC-based therapeutical approaches in regenerative medicine. [ABSTRACT FROM AUTHOR]

We consider organisms which use a renewal strategy such as run-tumble when moving in space, for example to perform chemotaxis in chemical gradients. We derive a diffusion approximation for the motion, applying a central limit theorem due to Anscombe for renewal-reward processes; this theorem has not previously been applied in this context. Our results extend previous work, which has established the mean drift but not the diffusivity. For a classical model of tumble rates applied to chemotaxis, we find that the resulting chemotactic drift saturates to the swimming velocity of the organism when the chemical gradients grow increasingly steep. The dispersal becomes anisotropic in steep gradients, with larger dispersal across the gradient than along the gradient. In contrast to one-dimensional settings, strong bias increases dispersal. We next include Brownian rotation in the model and find that, in limit of high chemotactic sensitivity, the chemotactic drift is 64 % of the swimming velocity, independent of the magnitude of the Brownian rotation. We finally derive characteristic timescales of the motion that can be used to assess whether the diffusion limit is justified in a given situation. The proposed technique for obtaining diffusion approximations is conceptually and computationally simple, and applicable also when statistics of the motion is obtained empirically or through Monte Carlo simulation of the motion. [ABSTRACT FROM AUTHOR]

Successful clinical outcomes from transplantation of hematopoietic stem cells (HSCs) depend upon efficient HSC homing to bone marrow (BM), subsequent engraftment, and, finally, BM repopulation. Homing of intravenously administered HSCs from peripheral blood (PB) through the circulation to the BM stem cell niches, which is the first critical step that precedes their engraftment, is enforced by chemotactic factors released in the BM microenvironment that chemoattract HSCs. These chemotactic factors include α-chemokine stromal-derived factor 1 (SDF-1), the bioactive phosphosphingolipids sphingosine-1-phosphate (S1P) and ceramid-1-phosphate (C1P), and the extracellular nucleotides ATP and UTP. Stem cells may also respond to a Ca or H gradient by employing calcium- or proton-sensing receptors, respectively. In this review, we will present emerging strategies based on ex vivo manipulation of graft HSCs that are aimed at enhancing the responsiveness of HSCs to BM-secreted chemoattractants and/or promoting HSC adhesion and seeding efficiency in the BM microenvironment. [ABSTRACT FROM AUTHOR]

Sex differences in behaviour extend to cognitive-like processes such as learning, but the underlying dimorphisms in neural circuit development and organization that generate these behavioural differences are largely unknown. Here we define at the single-cell level-from development, through neural circuit connectivity, to function-the neural basis of a sex-specific learning in the nematode Caenorhabditis elegans. We show that sexual conditioning, a form of associative learning, requires a pair of male-specific interneurons whose progenitors are fully differentiated glia. These neurons are generated during sexual maturation and incorporated into pre-exisiting sex-shared circuits to couple chemotactic responses to reproductive priorities. Our findings reveal a general role for glia as neural progenitors across metazoan taxa and demonstrate that the addition of sex-specific neuron types to brain circuits during sexual maturation is an important mechanism for the generation of sexually dimorphic plasticity in learning. [ABSTRACT FROM AUTHOR]

This paper deals with an initial-boundary value problem for the chemotaxis system under homogeneous Neumann boundary conditions in a convex smooth bounded domain $${\Omega\subset \mathbb{R}^n}$$ with $${n\geq3}$$ , where the diffusion function D( u) satisfying with some c > 0 and m > 1. The main goal of this paper was to extend a previous result on global existence of solutions by Wang et al. (Z Angew Math Phys 65:1137-1152, ) under the condition that $${m > 2-\frac{2}{n}}$$ can be relaxed to $${m > 2-\frac{6}{n+4}}$$ . [ABSTRACT FROM AUTHOR]

The gene encoding PTPROt (truncated isoform of protein tyrosine phosphatase receptor-type O) is methylated and suppressed in chronic lymphocytc leukemia (CLL). PTPROt exhibits in vitro tumor-suppressor characteristics through the regulation of B-cell receptor (BCR) signaling. Here we generated transgenic (Tg) mice with B-cell-specific expression of PTPROt. Although lymphocyte development is normal in these mice, crossing them with TCL1 Tg mouse model of CLL results in a survival advantage compared with the TCL1 Tg mice. Gene expression profiling of splenic B-lymphocytes before detectable signs of CLL followed by Ingenuity Pathway Analysis revealed that the most prominently regulated functions in TCL1 Tg vs non-transgenic (NTg) and TCL1 Tg vs PTPROt/TCL1 double Tg are the same and also biologically relevant to this study. Further, enhanced expression of the chemokine Ccl3, the oncogenic transcription factor Foxm1 and its targets in TCL1 Tg mice were significantly suppressed in the double Tg mice, suggesting a protective function of PTPROt against leukemogenesis. This study also showed that PTPROt-mediated regulation of Foxm1 involves activation of p53, a transcriptional repressor of Foxm1, which is facilitated through suppression of BCR signaling. These results establish the in vivo tumor-suppressive function of PTPROt and identify p53/Foxm1 axis as a key downstream effect of PTPROt-mediated suppression of BCR signaling. [ABSTRACT FROM AUTHOR]

Over the past two decades, fungal infections have emerged as significant causes of morbidity and mortality in patients with hematological malignancies, hematopoietic stem cell or solid organ transplantation and acquired immunodeficiency syndrome. Besides neutrophils and CD4 T lymphocytes, which have long been known to play an indispensable role in promoting protective antifungal immunity, mononuclear phagocytes are now being increasingly recognized as critical mediators of host defense against fungi. Thus, a recent surge of research studies has focused on understanding the mechanisms by which resident and recruited monocytes, macrophages and dendritic cells accumulate and become activated at the sites of fungal infection. Herein, we critically review how a variety of G-protein coupled chemoattractant receptors and their ligands mediate mononuclear phagocyte recruitment and effector function during infection by the most common human fungal pathogens. [ABSTRACT FROM AUTHOR]

The role of non-diagnostic features in the pathophysiology of autism spectrum disorders (ASDs) is unclear. Increasing evidence suggests immune system alterations in ASD may be implicated in the severity of behavioral impairment and other developmental outcomes. The primary objective of this meta-analysis was to investigate if there is a characteristic abnormal cytokine profile in ASD compared with healthy controls (HCs). We identified relevant studies following a search of MEDLINE, EMBASE, PsycINFO, Web of Knowledge and Scopus. A meta-analysis was performed on studies comparing plasma and serum concentrations of cytokines in unmedicated participants with ASD and HCs. Results were reported according to PRISMA statement. Seventeen studies with a total sample size of 743 participants with ASD and 592 HC were included in the analysis. Nineteen cytokines were assessed. Concentrations of interleukin (IL)-1beta (P<0.001), IL-6 (P=0.03), IL-8 (P=0.04), interferon-gamma (P=0.02), eotaxin (P=0.01) and monocyte chemotactic protein-1 (P<0.05) were significantly higher in the participants with ASD compared with the HC group, while concentrations of transforming growth factor-β1 were significantly lower (P<0.001). There were no significant differences between ASD participants and controls for the other 12 cytokines analyzed. The findings of our meta-analysis identified significantly altered concentrations of cytokines in ASD compared to HCs, strengthening evidence of an abnormal cytokine profile in ASD where inflammatory signals dominate. [ABSTRACT FROM AUTHOR]

It is well known that Escherichia coli executes chemotactic motion in response to chemical cues by modulating the flagellar motor bias alone. However, previous studies have reported the possibility of variation in run speed in the presence of attractants although it is unclear whether bacteria can deliberately modulate their swimming speeds in response to environmental cues or if the motor speeds are hardwired. By studying the detailed motion of cells in a uniform concentration of glucose and its non-metabolizable analogue, we show that changing concentrations may be accompanied by variation in the swimming speed. For a fixed run duration, cells exposed to the attractants achieved a higher peak-swimming speed after a tumble compared with that in plain motility buffer. Our experiments using the mutant strain lacking the Trg sensor show no change in swimming speed with varying concentrations of the non-metabolizable analogue, suggesting that sensing may play a role in the observed variation of swimming speed. [ABSTRACT FROM AUTHOR]

Inflammatory mediators have been studied in migraine pathophysiology; however, their role is not yet well established. The aim of the present study was to investigate interictal chemokine levels and its association with clinical parameters and psychiatric comorbidities in migraine patients compared with controls. This was a cross-sectional study including age and gender matched migraine patients and controls. Beck Depression and Anxiety Inventories, Headache Impact Test, and Allodynia Symptom Checklist were recorded. Chemokines were measured by ELISA. Forty-nine migraine patients and forty-nine controls without headache were included. CXCL8/IL-8 and CCL3/MIP-1α levels were significantly higher among patients with migraine ( P = 0.039 and 0.02, respectively) even after controlling for anxiety and depression scores. Chemokine levels were not correlated with migraine impact as well as allodynia scores. CXCL8/IL-8 and CCL3/MIP-1 α levels were raised in migraine, independently of psychiatric comorbidities, migraine impact, and allodynia. [ABSTRACT FROM AUTHOR]

Activation of complement cascade (ComC) play and important role in mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). While there are vast experimental data on the mechanisms and factors that induce or promote mobilization of HSPCs, there is relatively less data on negative regulators of this process. We demonstrate for the first time that heme oxygenase-1 (HO-1) that has a well-documented anti-inflammatory potential plays an important and heretofore unrecognized role in retention of HSPCs in BM niches by i) modulating negatively activation of mobilization promoting ComC, ii) maintaining stromal derived factor-1 (SDF-1) level in the BM microenvironment and iii) attenuating chemotactic responsiveness of HSPCs to SDF-1 and sphingosine-1 phosphate (S1P) gradients in PB. Furthermore, our data showing a positive mobilizing effect by a non-toxic small-molecule inhibitor of HO-1 (SnPP) suggest that blockade of HO-1 would be a promising strategy to facilitate mobilization of HSPCs. Further studies are also needed to evaluate better the molecular mechanisms responsible for the potential effect of HO-1 in homing of HSPCs after transplantation. [ABSTRACT FROM AUTHOR]

The aim is to study the anticancer effect of CXCR4 gene knockdown by CXCR4-siRNA in nude mice model of ovarian cancer. Injecti the SW626 tumor cells which had been transfected by vectors to make nude mouse model of ovarian cancer. The model mice were divided into interference group, negative control group, and blank control group. When the level of target genes were knocked down, the tumor volume was monitored and the tumor quality was measured; the expression of CXCR4 gene in the xenograft tumor was detected by RT-PCR, Western blot, and immunohistochemical staining. Nude mice model with implanted tumor were built successfully, after observing for 20 days. While the CXCR4 was knocked down, the abilities of invasion were weakened; the tumor volume and the tumor quality were also decreased. The CXCR4 mRNA and protein of the interference group decreased significantly ( P < 0.05). The animal experiment was confirmed that silencing of CXCR4 gene by siRNA can obviously inhibit the tumorigenesis of ovarian cancer. Our work will provide the theoretical basis for genes interference therapy of ovarian cancer in future. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are proposed as a promising source for cell-based therapies in neural disease. Although increasing numbers of studies have been devoted to the delineation of factors involved in the migration of MSCs, the relationship between the chemotactic response and the differentiation status of these cells is still unclear. In the present study, we demonstrated that MSCs in varying neural differentiation states display various chemotactic responses to stromal cell-derived factor-1α (SDF-1α). The chemotactic responses of MSCs under different differentiation stages in response to SDF-1α were analyzed by Boyden chamber, and the results showed that cells of undifferentiation, 24-h preinduction, 5-h induction, and 18-h maintenance states displayed a stronger chemotactic response to SDF-1α, while 48-h maintenance did not. Further, we found that the phosphorylation levels of PI3K/Akt, ERK1/2, SAPK/JNK, and p38MAPK are closely related to the differentiation states of MSCs subjected to SDF-1α, and finally, inhibition of SAPK/JNK signaling significantly attenuates SDF-1α-stimulated transfilter migration of MSCs of undifferentiation, 24-h preinduction, 18-h maintenance, and 48-h maintenance, but not MSCs of 5-h induction. Meanwhile, interference with PI3K/Akt, p38MAPK, or ERK1/2 signaling prevents only cells at certain differentiation state from migrating in response to SDF-1α. Collectively, these results demonstrate that MSCs in varying neural differentiation states have different migratory capacities, thereby illuminating optimization of the therapeutic potential of MSCs to be used for neural regeneration after injury. [ABSTRACT FROM AUTHOR]

Introduction: Intense resistance exercise causes mechanical loading of skeletal muscle, followed by muscle adaptation. Chemotactic factors likely play an important role in these processes. Purpose: We investigated the time course of changes in the expression and tissue localization of several key chemotactic factors in skeletal muscle during the early phase of recovery following resistance exercise. Methods: Muscle biopsy samples were obtained from vastus lateralis of eight untrained men (22 ± 0.5 years) before and 2, 4 and 24 h after three sets of leg press, squat and leg extension at 80 % 1-RM. Results: Monocyte chemotactic protein-1 (95×), interleukin-8 (2,300×), IL-6 (317×), urokinase-type plasminogen activator (15×), vascular endothelial growth factor (2×) and fractalkine (2.5×) mRNA was significantly elevated 2 h post-exercise. Interleukin-8 (38×) and interleukin-6 (58×) protein was also significantly elevated 2 h post-exercise, while monocyte chemotactic protein-1 protein was significantly elevated at 2 h (22×) and 4 h (21×) post-exercise. Monocyte chemotactic protein-1 and interleukin-8 were expressed by cells residing in the interstitial space between muscle fibers and, in some cases, were co-localized with CD68 + macrophages, PAX7 + satellite cells and blood vessels. However, the patterns of staining were inconclusive and not consistent. Conclusion: In conclusion, resistance exercise stimulated a marked increase in the mRNA and protein expression of various chemotactic factors in skeletal muscle. Myofibers were not the dominant source of these factors. These findings suggest that chemotactic factors regulate remodeling/adaptation of skeletal muscle during the early phase of recovery following resistance exercise. [ABSTRACT FROM AUTHOR]

We consider nonnegative solutions of the Neumann initial-boundary value problem for the chemotaxis-growth system in $$\Omega :=(0,L)\subset \mathbb {R}$$ with $$L>0, \varepsilon >0, r\ge 0$$ and $$\mu >0$$ , along with the corresponding limit problem formally obtained upon taking $$\varepsilon \searrow 0$$ . For the latter hyperbolic-elliptic problem, we establish results on local existence and uniqueness within an appropriate generalized solution concept. In this context we shall moreover derive an extensibility criterion involving the norm of $$u(\cdot ,t)$$ in $$L^\infty (\Omega )$$ . This will enable us to conclude that in this case $$\varepsilon =0$$ , The latter will reveal that the original parabolic-elliptic problem ( $$\star $$ ), though known to possess no such exploding solutions, exhibits the following property of dynamical structure generation: given any $$\mu \in (0,1)$$ , one can find smooth bounded initial data with the property that for each prescribed number $$M>0$$ the solution of ( $$\star $$ ) will attain values above $$M$$ at some time, provided that $$\varepsilon $$ is sufficiently small. In particular, this means that the associated carrying capacity given by $$\frac{r}{\mu }$$ can be exceeded during evolution to an arbitrary extent. We finally present some numerical simulations that illustrate this type of solution behavior and that, moreover, inter alia, indicate that achieving large population densities is a transient dynamical phenomenon occurring on intermediate time scales only. [ABSTRACT FROM AUTHOR]

Chemotaxis, or directed migration of cells along a chemical gradient, is a highly coordinated process that involves gradient sensing, motility, and polarity. Most of our understanding of chemotaxis comes from studies of cells undergoing amoeboid-type migration, in particular the social amoeba Dictyostelium discoideum and leukocytes. In these amoeboid cells the molecular events leading to directed migration can be conceptually divided into four interacting networks: receptor/G protein, signal transduction, cytoskeleton, and polarity. The signal transduction network occupies a central position in this scheme as it receives direct input from the receptor/G protein network, as well as feedback from the cytoskeletal and polarity networks. Multiple overlapping modules within the signal transduction network transmit the signals to the actin cytoskeleton network leading to biased pseudopod protrusion in the direction of the gradient. The overall architecture of the networks, as well as the individual signaling modules, is remarkably conserved between Dictyostelium and mammalian leukocytes, and the similarities and differences between the two systems are the subject of this review. [ABSTRACT FROM AUTHOR]

We solve the problem of first-passage time for run-and-tumble particles in one dimension. Exact expression is derived for the mean first-passage time in the general case, considering external force fields and chemotactic fields, giving rise to space-dependent swim speed and tumble rate. Agreement between theoretical formulae and numerical simulations is obtained in the analyzed case studies --constant and sinusoidal force fields, constant gradient chemotactic field. Reported findings can be useful to get insights into very different phenomena involving active particles, such as bacterial motion in external fields, intracellular transport, cell migration, animal foraging. Graphical abstract: [ABSTRACT FROM AUTHOR]

Angiogenesis plays a key role in bone formation and maintenance. Bone formation has been reported to initiate in the concavities rather than the convexities in a hydroxyapatite substratum and the implant threads of dental implants. The aim of the present study was to evaluate the number of the blood vessels inside the concavities and around the convexities of the threads of implants in a rabbit tibia model. A total of 32 thread-shaped implants blasted with apatitic calcium phosphate (TCP/HA blend) (Resorbable Blast Texturing, RBT) (Maestro, BioHorizons, Birmingham, AL, USA) were inserted in 8 rabbits. Each rabbit received 4 implants, 2 in the right and 2 in left tibia. Implants were retrieved after 1, 2, 4, and 8 weeks and treated to obtain thin ground sections. Statistically significant differences were found in the number of vessels that had formed in the concavities rather than the convexities of the implants after 1 ( p = 0.000), and 2 weeks ( p = 0.000), whilst no significant differences after 4 ( p = 0.546) and 8 weeks ( p = 0.275) were detected. The present results supported the hypothesis that blood vessel formation was stimulated by the presence of the concavities, which may provide a suitable environment in which mechanical forces, concentrations and gradients of chemotactic molecules and blood clot retention may all drive vascular and bone cell migration. [ABSTRACT FROM AUTHOR]

Deletion of 3p12-22 is frequent in multiple cancer types, indicating the presence of critical tumor-suppressor genes (TSGs) at this region. We studied a novel candidate TSG, CMTM7, located at the 3p22.3 CMTM-gene cluster, for its tumor-suppressive functions and related mechanisms. The three CMTM genes, CMTM6, 7 and 8, are broadly expressed in human normal adult tissues and normal epithelial cell lines. Only CMTM7 is frequently silenced or downregulated in esophageal and nasopharyngeal cell lines, but uncommon in other carcinoma cell lines. Immunostaining of tissue microarrays for CMTM7 protein showed its downregulation or absence in esophageal, gastric, pancreatic, liver, lung and cervix tumor tissues. Promoter CpG methylation and loss of heterozygosity were both found contributing to CMTM7 downregulation. Ectopic expression of CMTM7 in carcinoma cells inhibits cell proliferation, motility and tumor formation in nude mice, but not in immortalized normal cells, suggesting a tumor inhibitory role of CMTM7. The tumor-suppressive function of CMTM7 is associated with its role in G1/S cell cycle arrest, through upregulating p27 and downregulating cyclin-dependent kinase 2 (CDK2) and 6 (CDK6). Moreover, CMTM7 could promote epidermal growth factor receptor (EGFR) internalization, and further suppress AKT signaling pathway. Thus, our findings suggest that CMTM7 is a novel 3p22 tumor suppressor regulating G1/S transition and EGFR/AKT signaling during tumor pathogenesis. [ABSTRACT FROM AUTHOR]

CheY is a chemotactic response regulator protein modulating the rotation direction of bacterial flagellar motors. It plays an important role in the colonization and infection of Helicobacter pylori ( H. pylori), which is a common pathogen. Recently, the structure of CheY1 of H. pylori (HpCheY1) was solved, showing similarities and differences with CheY from E. coli. Here, we report 200 ns atomistic molecular dynamics (MD) simulations of HpCheY1 and two mutants. The results suggest that the surface of HpCheY1 has regions with increased affinity for Mg. In addition, wildtype HpCheY1 (WT HpCheY1) shows characteristic dynamics in helix 4, which is involved in FliM binding. This dynamics is altered in the D53A mutant and completely suppressed in the T84A mutant. The results are discussed in relation to the binding and function of HpCheY1. [ABSTRACT FROM AUTHOR]

Bacterial foraging optimization (BFO) is predominately used to find solutions for real-world problems. One of the major characteristics of BFO is the chemotactic movement of a virtual bacterium that models a trial solution of the problems. It is pointed out that the chemotaxis employed by classical BFO usually results in sustained oscillation, especially on rough fitness landscapes, when a bacterium cell is close to the optima. In this paper we propose a novel adaptive computational chemotaxis based on the concept of field, in order to accelerate the convergence speed of the group of bacteria near the tolerance. Firstly, a simple scheme is designed for adapting the chemotactic step size of each field. Then, the scheme chooses the fields which perform better to boost further the convergence speed. Empirical simulations over several numerical benchmarks demonstrate that BFO with adaptive chemotactic operators based on field has better convergence behavior, as compared against other meta-heuristic algorithms. [ABSTRACT FROM AUTHOR]

Angiostrongylus cantonensis invasion primarily cause heavy or negligible eosinophic meningitis and meningoencephalitis in the brain of non-permissive and permissive hosts, respectively. Chemokines are effective leukocyte chemoattractants and may play an essential role in mediating eosinophil recruitment in angiostrongyliasis. In the present study, we comparatively analyzed changes in peripheral and CSF eosinophil counts, and expression profilings of eosinophil chemotactic chemokines in A. cantonensis-infected mice (CCL 2, CCL 3, CCL 5, CCL7, CCL 8, CCL 11, CCL 12, CCL 24 and CCL 28) and rats (CCL 2, CCL 3, CCL 5, CCL 11 and CCL 12) were explored at 1, 2, 5, 7, 14, and 21 days post-infection (dpi), and found significantly elevated numbers of eosinophils in blood and CSF of infected mice after 5 dpi, while significant increases of eosinophils in blood and CSF of infected rats were detected after 5 and 14 dpi, respectively. The kinetics of CSF eosinophilia is basically correlated with eosinophil chemotactic chemokine levels in brains of infected animals at each time point. Interestingly, less CSF eosinophils and infiltration of eosinophils in the brain were noted in rats than in mice, though extremely high levels of chemokines were also maintained in the brains of infected rats at 21 dpi. We further described CCL 11 (eotaxin), a previously reported eosinophil chemotactic factor in angiostrongyliasis, was mainly released from activated microglia in mice and rats infected with A. cantonensis. Our results reveal that different complicated chemokine networks mediate recruitment of eosinophils between permissive and non-permissive hosts during A. cantonensis infection, and provide promising targets for clinical treatment of angiostrongyliasis. [ABSTRACT FROM AUTHOR]

We propose a bacteria-based microrobot (bacteriobot) based on a new fusion paradigm for theranostic activities against solid tumors. We develop a bacteriobot using the strong attachment of bacteria to Cy5.5-coated polystyrene microbeads due to the high-affinity interaction between biotin and streptavidin. The chemotactic responses of the bacteria and the bacteriobots to the concentration gradients of lysates or spheroids of solid tumors can be detected as the migration of the bacteria and/or the bacteriobots out of the central region toward the side regions in a chemotactic microfluidic chamber. The bacteriobots showed higher migration velocity toward tumor cell lysates or spheroids than toward normal cells. In addition, when only the bacteriobots were injected to the CT-26 tumor mouse model, Cy5.5 signal was detected from the tumor site of the mouse model. In-vitro and in-vivo tests verified that the bacteriobots had chemotactic motility and tumor targeting ability. The new microrobot paradigm in which bacteria act as microactuators and microsensors to deliver microstructures to tumors can be considered a new theranostic methodology for targeting and treating solid tumors. [ABSTRACT FROM AUTHOR]

The directed migration of cell collectives is a driving force of embryogenesis. The predominant view in the field is that cells in embryos navigate along pre-patterned chemoattractant gradients. One hypothetical way to free migrating collectives from the requirement of long-range gradients would be through the self-generation of local gradients that travel with them, a strategy that potentially allows self-determined directionality. However, a lack of tools for the visualization of endogenous guidance cues has prevented the demonstration of such self-generated gradients in vivo. Here we define the in vivo dynamics of one key guidance molecule, the chemokine Cxcl12a, by applying a fluorescent timer approach to measure ligand-triggered receptor turnover in living animals. Using the zebrafish lateral line primordium as a model, we show that migrating cell collectives can self-generate gradients of chemokine activity across their length via polarized receptor-mediated internalization. Finally, by engineering an external source of the atypical receptor Cxcr7 that moves with the primordium, we show that a self-generated gradient mechanism is sufficient to direct robust collective migration. This study thus provides, to our knowledge, the first in vivo proof for self-directed tissue migration through local shaping of an extracellular cue and provides a framework for investigating self-directed migration in many other contexts including cancer invasion. [ABSTRACT FROM AUTHOR]

Characterizing the chemotactic motility of slowly migrating cells as a function of time is still challenging. In this paper, we use a microfluidic device for investigating the chemotactic activity of HFF-1 fibroblasts in a sigmoidal concentration profile of epidermal growth factor (EGF). Sigmoidal concentration profiles are very common in biological systems but, in contrast to linear gradients, are much less studied in microfluidic systems. We monitored cell migration for up to 10 hours and found that chemotaxis is strongest where the absolute EGF concentration is below 25 pM ( K of EGF is 1 nM). Calculating the fraction of receptor occupancy ( FRO) at the front and rear of the cells showed that the chemotactic activity of HFF-1 cells scaled with the difference in FRO between both ends of the cell normalized by the average FRO of the cell. Interestingly, the mean chemotactic index of the cells was found to be a function of the gradient at the starting position and did not change when cells were entering into other regions of the highly non-linear concentration profile. Our studies demonstrate the usefulness of stable sigmoidal concentration profiles produced in microfluidic channels for a detailed analysis of the chemotactic response of slowly migrating cells. [ABSTRACT FROM AUTHOR]

Failure of remyelination of multiple sclerosis (MS) lesions contributes to neurodegeneration that correlates with chronic disability in patients. Currently, there are no available treatments to reduce neurodegeneration, but one therapeutic approach to fill this unmet need is to promote remyelination. As many demyelinated MS lesions contain plentiful oligodendrocyte precursor cells (OPCs), but no mature myelinating oligodendrocytes, research has previously concentrated on promoting OPC maturation. However, some MS lesions contain few OPCs, and therefore, remyelination failure may also be secondary to OPC recruitment failure. Here, in a series of MS samples, we determined how many lesions contained few OPCs, and correlated this to pathological subtype and expression of the chemotactic molecules Semaphorin (Sema) 3A and 3F. 37 % of MS lesions contained low numbers of OPCs, and these were mostly chronic active lesions, in which cells expressed Sema3A (chemorepellent). To test the hypothesis that differential Sema3 expression in demyelinated lesions alters OPC recruitment and the efficiency of subsequent remyelination, we used a focal myelinotoxic mouse model of demyelination. Adding recombinant (r)Sema3A (chemorepellent) to demyelinated lesions reduced OPC recruitment and remyelination, whereas the addition of rSema3F (chemoattractant), or use of transgenic mice with reduced Sema3A expression increased OPC recruitment and remyelination. We conclude that some MS lesions fail to remyelinate secondary to reduced OPC recruitment, and that chemotactic molecules are involved in the mechanism, providing a new group of drug targets to improve remyelination, with a specific target in the Sema3A receptor neuropilin-1. [ABSTRACT FROM AUTHOR]

Spleen-resident dendritic cell (DC) populations occupy sentinel positions for the capture and presentation of blood-borne antigens. Here we found a difference in expression of the chemotactic receptor EBI2 (GPR183) on splenic DC subsets and that EBI2 regulated the positioning and homeostasis of DCs in the spleen. EBI2 and its main ligand, 7α,25-OHC, were required for the generation of the splenic CD4+ DC subset and the localization of DCs in bridging channels. Absence of EBI2 from DCs resulted in defects in both the activation of CD4+ T cells and the induction of antibody responses. Regulated expression of EBI2 on DC populations is therefore critical for the generation and correct positioning of splenic DCs and the initiation of immune responses. [ABSTRACT FROM AUTHOR]